The interaction of cadmium with metallothionein, a low molecular weight cysteine-rich cadmium binding protein, will be investigated by 113Cd, 13C, and 1H NMR. This multinuclear NMR study should provide the detailed structural information needed to define the chemical nature of the cadmium binding sites. Since metallothionein is suspected to play an important, though poorly characterized, physiological role in metal detoxification, metabolism, and/or transport, such structural information may be expected to lead to an understanding of the nature of cadmium toxicity and the mechanisms by which cadmium is handled by various organisms in the biosphere. The experimental approach will be to completely define the structural state of native rabbit liver metallothionein induced by 113Cd2 ion injection in terms of its 113Cd, 13C, and 1H NMR parameters. Preliminary 113Cd NMR results indicate that the metal ions are arranged in a polynuclear cluster arrangement in the protein. The structural details of these metal clusters will be investigated by homonuclear decoupling and spin echo techniques. Spin relaxation studies will be carried out to provide dynamic information such as metal and ligand exchange rates. To explore questions relating to the function of metallothionein, the rabbit liver protein will be compared with protein from different tissues and species.